Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT biopsies from healthy normal weight individuals (BMI 18.5 to 25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30 to 40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g EPA + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide and eicosapentaenoyl ethanolamide), higher expression of PLA2G2D and PLA2G4A, and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT eicosapentaenoyl ethanolamide and docosahexaenoyl ethanolamide increased in normal weight individuals only and WAT 2-arachidonyl glycerol decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.